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1.
Seizure ; 117: 44-49, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308908

RESUMO

OBJECTIVE: Perampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4-18 years) with epilepsy. METHOD: A multicenter prospective observational study was performed on children and adolescents (age, 4-18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. RESULTS: In this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. CONCLUSION: The overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.


Assuntos
Anticonvulsivantes , Quimioterapia Combinada , Epilepsia , Nitrilas , Piridonas , Humanos , Criança , Masculino , Feminino , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Piridonas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Adolescente , Pré-Escolar , Estudos Prospectivos , Epilepsia/tratamento farmacológico , Resultado do Tratamento
2.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33215218

RESUMO

S100a8 serves an important role in cell differentiation and is abnormally expressed in common tumors, but there are few studies on the association between S100a8 and brain I/R injury. The present study aimed to investigate the role of S100a8 in oxygen­glucose deprivation and reoxygenation (OGD/R)­induced BV2 microglia cell injury, and to elucidate the potential underlying molecular mechanisms. BV2 cells were exposed to OGD/R to mimic ischemia/reperfusion (I/R) injury in vitro. S100a8 expression was detected via reverse transcription­quantitative PCR and western blot analyses. Following transfection with short hairpin RNAs targeting S100a8, the levels of inflammatory cytokines and oxidative stress­related factors were determined using commercial kits. Apoptosis was assessed using flow cytometric analysis and the expression levels of apoptosis­related proteins were determined using western blot analysis. Subsequently, the mRNA and protein levels of Grb2­associated binder 1 (GAB1) were assessed following S100a8 silencing. Immunoprecipitation (IP) was performed to verify the association between S100a8 and GAB1. The levels of inflammation, oxidative stress and apoptosis were assessed following GAB1 silencing, along with S100a8 silencing in BV2 cells subjected to OGD/R. The results indicated that exposure to OGD/R markedly upregulated S100a8 expression in BV2 cells. S100a8 silencing inhibited inflammation, oxidative stress and apoptosis, accompanied by changes in the expression of related proteins. The IP assay revealed a strong interaction between GAB1 and S100a8. In addition, GAB1 silencing reversed the inhibitory effects of S100a8 silencing on inflammation, oxidative stress and apoptosis in OGD/R­stimulated BV2 cells. Taken together, the results of the present study demonstrated that S100a8 silencing alleviated inflammation, oxidative stress and the apoptosis of BV2 cells induced by OGD/R, partly by upregulating the expression of GAB1. Thus, these findings may potentially provide a novel direction to develop therapeutic strategies for cerebral I/R injury.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Calgranulina A/metabolismo , Inflamação/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose/genética , Calgranulina A/genética , Linhagem Celular , Inativação Gênica , Glucose/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação/genética , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Camundongos , Microglia/metabolismo , Estresse Oxidativo/genética , Oxigênio/metabolismo , Traumatismo por Reperfusão/etiologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
3.
Medicine (Baltimore) ; 99(17): e19968, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332682

RESUMO

INTRODUCTION: Hyperekplexia is a rare hereditary neurological disorder; only 5 glycine receptor alpha 1 subunit gene (GLRA1) mutations have been reported in 5 Chinese patients. We report a Chinese infant with hyperekplexia and a novel mutation at c.292G > A. PATIENT CONCERNS: A Chinese infant with hyperekplexia and a novel mutation at c.292G > A. DIAGNOSIS: All exons of GLRA1 were sequenced in her parents and her, which revealed a mutation at c.1030C > T and another novel mutation at c.292G > A. Her diagnosis was confirmed as hereditary hyperekplexia with GlRA1 hybrid gene mutations based on the sequencing results. INTERVENTIONS: She was treated with clonazepam. OUTCOMES: Her muscle hypertonia recovered rapidly and the excessive startle reflex to unexpected stimuli was significantly reduced. CONCLUSION: Genetic DNA sequencing is a crucial method for diagnosing hyperekplexia-related gene mutation.


Assuntos
Receptores de Glicina/genética , Rigidez Muscular Espasmódica/genética , China , Clonazepam/uso terapêutico , Feminino , Humanos , Lactente , Mutação/genética , Reflexo de Sobressalto/efeitos dos fármacos , Rigidez Muscular Espasmódica/tratamento farmacológico
4.
Sci China Life Sci ; 60(4): 404-416, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27921235

RESUMO

Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.


Assuntos
Células da Medula Óssea/metabolismo , Transplante de Células , Colágeno/metabolismo , Regulação para Baixo , Endométrio/patologia , Ginatresia/metabolismo , Alicerces Teciduais , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Feminino , Humanos , Reação em Cadeia da Polimerase em Tempo Real
5.
PLoS One ; 10(4): e0124001, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25853857

RESUMO

Balanced immune responses are essential for the maintenance of successful pregnancy. Aberrant responses of immune system during pregnancy increase the risk of preeclampsia. Toll-like receptor 4 (TLR4) plays a crucial role in the activation of immune system at the maternal-fetal interface. This study aimed to generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist) administration on gestational day (GD) 5 as rats are subjected to placentation immediately after implantation between GDs 4 and 5, and to assess the contribution of TLR4 signaling to the development of preeclampsia. Single administration of 0.5 µg/kg LPS significantly increased blood pressure of pregnant rats since GD 6 (systolic blood pressure, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05) and urinary protein level since GD 9 (2.02 ± 0.29 mg versus 1.11 ± 0.18 mg, P < 0.01), but barely affected blood pressure or proteinuria of virgin rats compared with those of saline-treated pregnant rats. This was accompanied with adverse pregnancy outcomes including fetal growth restriction. The expression of TLR4 and NF-κB p65 were both increased in the placenta but not the kidney from LPS-treated pregnant rats, with deficient trophoblast invasion and spiral artery remodeling. Furthermore, the levels of inflammatory cytokines were elevated systemically and locally in the placenta from pregnant rats treated with LPS. TLR4 signaling in the placenta was activated, to which that in the placenta of humans with preeclampsia changed similarly. In conclusion, LPS administration to pregnant rats in early pregnancy could elicit TLR4-mediated immune response at the maternal-fetal interface contributing to poor early placentation that may culminate in the preeclampsia-like syndrome.


Assuntos
Modelos Animais de Doenças , Lipopolissacarídeos/administração & dosagem , Placenta/imunologia , Pré-Eclâmpsia/imunologia , Ratos , Receptor 4 Toll-Like/imunologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Feto , Regulação da Expressão Gênica , Humanos , Injeções Intravenosas , Placenta/irrigação sanguínea , Placenta/efeitos dos fármacos , Placenta/fisiopatologia , Placentação/efeitos dos fármacos , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/fisiopatologia , Gravidez , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/agonistas , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologia
6.
Eye Sci ; 28(4): 180-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24961089

RESUMO

PURPOSE: To investigate the clinical characteristics and therapeutic effects of vitrectomy in patients with perforating eye injuries with foreign bodies at the exit wound in the posterior global wall. METHODS: Fifty-two cases, diagnosed with perforating eye injury with foreign bodies at the exit of the posterior global wall and admitted to our hospital between June 2010 and June 2013, were enrolled in this study. All patients underwent vitrectomy and removal of intraocular foreign bodies and were followed up for 6 to 24 months. The causes of injuries were analyzed and postoperative visual acuity and overall treatment efficacy were evaluated. RESULTS: Intraocular foreign bodies were successfully removed in all cases. The incidence of postoperative complication was low. Among 52 subjects, 46 showed alleviated symptoms after treatment with an overall efficacy of 88.46%. CONCLUSION: Perforating eye injuries combined with residual foreign bodies in the posterior global wall are commonly observed in young people who perform physical labor. Vitrectomy has a high efficacy for the treatment of perforating eye injuries complicated with foreign bodies located at the posterior global wall, with a low incidence of postoperative complications.


Assuntos
Corpos Estranhos no Olho/cirurgia , Ferimentos Oculares Penetrantes/cirurgia , Vitrectomia , Corpos Estranhos no Olho/complicações , Ferimentos Oculares Penetrantes/complicações , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Acuidade Visual
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